Warfarin or Antiplatelet Therapy for Stroke Prevention in Patients with Non-Valvular Atrial Fibrillation

A systematic review 1 included 29 studies with a total of 28044 subjects (mean age 71 years, mean follow-up 1.5 years). The average stroke rate for untreated (placebo or control group) patients was 13% per year in secondary prevention trials (patients with previous stroke or TIA) and 4.1% per year for those in primary prevention trials. Adjusted-dose warfarin reduced stroke by 64% (95% CI 49 to 74%; 6 studies, n=2900) compared with control and the absolute risk reduction was 2.7% per year for primary prevention (NNT 37; 27 strokes prevented when treated 1000 patients for 1 year) and 8.4% for secondary prevention (NNT 12; 83/1000). Antiplatelet agents reduced stroke by 22% (95% CI 6 to 35%; 8 studies, n=4876). 7 studies (n=3990) compared aspirin with placebo or no treatment; aspirin was associated with a 19% (95% CI -1% to 35%) reduced incidence of stroke. The absolute risk reduction was 0.8% per year (NNT 125; 8/1000) for primary prevention and 2.5% per year (NNT 40; 25/1000) for secondary prevention.

Adjusted-dose warfarin was more efficacious than antiplatelet therapy (relative risk reduction 39%, 95% CI 22 to 52%; 12 studies, n=12 963). The point estimate of the relative risk reduction was similar when compared with clopidogrel plus aspirin (40%, 1 study) and with pooled results from 8 studies of aspirin alone (38%). There were only 2 RCTs that added antiplatelet therapy to full-dose anticoagulant therapy and thus, there is insufficient evidence on the efficacy and safety of such therapy.

The risk of intracranial hemorrhage was doubled with adjusted-dose warfarin compared with aspirin, but the absolute risk increase was small (0.2% per year). Intracranial hemorrhage was included with as all strokes and was considered in the primary analysis. Absolute increase in major extracranial hemorrhage with warfarin compared to aspirin also was small (0.2% per year).

These results are consistent with the results of Cochrane reviews [Abstract] 2 [Abstract] 3[Abstract] 4[Abstract] 5[Abstract] 6 on the same topic.

Comment: In clinical practice for warfarin-naive and older patients, the benefits and risks of anticoagulation therapy may not be identical to the results obtained from RCTs (bleeding risk may be higher).

References

• Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007 Jun 19;146(12):857-67. [PubMed]
• Aguilar MI, Hart R, Pearce LA. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2007 Jul 18;(3):CD006186. [PubMed].
• Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2005 Jul 20;(3):CD001927. [PubMed]
• Aguilar M, Hart R. Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2005 Oct 19;(4):CD001925. [PubMed].
• Saxena R, Koudstaal PJ. Anticoagulants for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischaemic attack. Cochrane Database Syst Rev 2004;(2):CD000185. [PubMed].
• Saxena R, Koudstaal P. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database Syst Rev 2004 Oct 18;(4):CD000187. [PubMed].